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First published online on January 11, 2008.
Experimental Physiology (2008)
DOI: 10.1113/expphysiol.2007.040204
© The Physiological Society 2008

A more recent version of this article appeared on May 1, 2008
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Received November 14, 2007
Revised December 7, 2007
Accepted after revision January 8, 2008


Vascular [310]

Co-localisation of ACE2, Oct-4 and CD34 positive cells in rabbit atherosclerotic plaques

A Zulli 1*, Sudarshan Rai 1, Brian Buxton 2, Louise Burrell 3, David Hare 3

1 Melbourne University
2 Austin Health
3 University of Melbourne

* To whom correspondence should be addressed. E-mail: azulli{at}unimelb.edu.au.


   Abstract
ACE2 is a novel enzyme with possible implications in the treatment of blood pressure. Recent evidence suggests that an upregulation of ACE2 can be stimulated by all trans retinoic acid (at-RA), however at-RA also affects Oct-4 regulation and thus cellular differentiation. We have previously shown in separate publications that smooth muscle cells and macrophages present within rabbit atherosclerotic plaques are positive for ACE2, the hematopoietic stem-cell marker CD34, and the stem cell marker Oct-4. Thus, to provide evidence that possible at-RA treatment could affect both plaque cellular biology via effects on cellular differentiation, as well as blood pressure via ACE2, it is vital to show that cells with atherosclerotic plaques co-express all three markers. Thus, we sought to provide evidence that a subset of cells within atherosclerotic plaques are positive for ACE2, Oct-4 and CD34. We used New Zealand White rabbits and were fed a control diet supplemented with 0.5% cholesterol plus 1% methionine for 4 weeks and then allowed to consume a normal diet for 10 weeks. Immunohistochemistry was performed by standard techniques. We repot that Oct-4, ACE2 and CD34 were all present within in atherosclerotic plaques. Although macrophages were positive for all three markers, spindle shaped cells in the media did not show all three markers. The endothelium overlying normal wall showed positive Oct-4 and ACE2 immunoreactivity, but CD34 immunoreactivity was patchy, indicating that such cells might not have fully differentiated. It is concluded that cells in atherosclerotic plaques express both ACE2, Oct-4 and CD34. Further studies aimed establishing the effects of all trans retinoic acid on blood pressure and atherosclerotic cell differentiation are warranted.

Key Words: Aorta, Endothelium, Pathology




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